The Experimental therapeutics in critical care postdoctoral training program proposal is designed to support a 5-year continuation of our existing multidisciplinary research training program. This proposal trains fellows, for a period of 2 or 3 years each, in the science of organ dysfunction and its consequences in critical illness. Funds to support 4 fellows for all years are requested. The overall research focus of the trainees is the biology of acute severe illness and its response to therapy in 3 inter-related levels of investigation: 1) Immunobiology and Cellular Basis for Organ Injury; 2) Organ-systems Modeling; and 3) Clinical and Health Services Research. This approach underscores the essential basis of critical care medicine, requiring an integration of cell and molecular biology t organ-system monitoring, and therapies to define their effects on socially relevant outcomes. These research areas coincide with extramural research grants of the training faculty. The research plans are excellent vehicles for training because they ask broad questions on which precise, well-targeted individual research training efforts can be staged. The faculty are an experienced and dedicated group of federally-funded senior academicians. Upon completion of the training program, the fellow will understand how to design, execute, and complete experiments to answer specific questions derived from critically ill patients. Thus, the fellow wil be also trained in the thought processes needed to apply these tools in the future as they relate to real life problems in critically ill patients. All trainees will take formal postgraduate course offered by the University of Pittsburgh and the year-long Responsible Conduct in Research program including small group discussion session. Some trainees may complete coursework necessary to receive PhD or MPH degrees. Most training will take place in the laboratories of the principal trainers using a carefully thought-out version of the time-honored master-apprentice system. This training technique combines weekly meetings between the trainee and trainer as well as weekly hour-long research training seminars at which the trainer group, including of the principal trainer and other research trainers, whose special skills and interests are chosen to supplement the principal trainer, concurrently guide and monitor the trainee's research program. Furthermore, formal research presentations by the trainees are given biannually to our formal Clinical Research, Investigation and Systems Modeling of Acute Illness (CRISMA) research community. This flexible but intense degree of supervision permits the simultaneous completion of efficient, cordial, and cooperative research and training. Individual fellows choose a principal trainer with the support and guidance of the Executive Training Committee. They collectively fashion an individualized training program, trainer group, and coursework program to allow the fellow to accomplish the educational and research goals of their program. Affirmative action recruitment efforts are already in place and effective. The training facilities can serve more fellows than will be funded by this proposal and all training wil be carried out in our fully equipped facilities.